New insights into the role of hilar ectopic granule cells in the dentate gyrus based on quantitative anatomic analysis and three-dimensional reconstruction

• Published in: Epilepsia (Copenhagen) 2012-06, Vol.53 (s1), p.109-115
• Main Authors: Scharfman, Helen E., Pierce, Joseph P.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Brain; Cytoplasmic Granules - pathology; Dentate Gyrus - pathology; Dentate Gyrus - physiology; Dentate Gyrus - ultrastructure; Epilepsy; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - etiology; Epilepsy, Temporal Lobe - pathology; Epileptogenesis; Excitatory Postsynaptic Potentials - drug effects; Granule cell; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hub cell; Hypoxia, Brain - complications; Hypoxia, Brain - pathology; Imaging, Three-Dimensional; Immunohistochemistry; Medical sciences; Microscopy, Immunoelectron; Microtubule-Associated Proteins - metabolism; Migration; Mossy fiber; Mossy Fibers, Hippocampal - pathology; Muscarinic Agonists; Nervous system (semeiology, syndromes); Neurology; Neuropeptides - metabolism; Neuropharmacology; Pharmacology. Drug treatments; Pilocarpine; Postnatal neurogenesis; Presynaptic Terminals - pathology; Rats; Seizures - pathology; Seizures - psychology; Sprouting; Synapses - pathology; Synapses - physiology; Synapses - ultrastructure
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2012.03480.x

Summary The dentate gyrus is one of two main areas of the mammalian brain where neurons are born throughout adulthood, a phenomenon called postnatal neurogenesis. Most of the neurons that are generated are granule cells (GCs), the major principal cell type in the dentate gyrus. Some adult‐born granule cells develop in ectopic locations, such as the dentate hilus. The generation of hilar ectopic granule cells (HEGCs) is greatly increased in several animal models of epilepsy and has also been demonstrated in surgical specimens from patients with intractable temporal lobe epilepsy (TLE). Herein we review the results of our quantitative neuroanatomic analysis of HEGCs that were filled with Neurobiotin following electrophysiologic characterization in hippocampal slices. The data suggest that two types of HEGCs exist, based on a proximal or distal location of the cell body relative to the granule cell layer, and based on the location of most of the dendrites, in the molecular layer or hilus. Three‐dimensional reconstruction revealed that the dendrites of distal HEGCs can extend along the transverse and longitudinal axis of the hippocampus. Analysis of axons demonstrated that HEGCs have projections that contribute to the normal mossy fiber innervation of CA3 as well as the abnormal sprouted fibers in the inner molecular layer of epileptic rodents (mossy fiber sprouting). These data support the idea that HEGCs could function as a “hub” cell in the dentate gyrus and play a critical role in network excitability.